We have previously proposed a model for the development of Alzheimer's disease (AD) that is based on the effects of choline leakage. According to the model, beta-amyloid causes leakage of choline across the plasma membrane of cholinergic cells, leading to a decrease in the choline concentration of the cells, and hence a decrease in their production of acetylcholine. The decrease in acetylcholine concentration, in turn, has previously been shown to cause an increase in the concentration of beta-amyloid. Thus, these reciprocal effects result in positive feedback and hence a faster loss of acetylcholine. A large loss of acetylcholine is a hallmark of AD. We are currently testing this model by determining whether there is significantly more choline leakage from AD brains than from control brains. To do this, we obtain brain tissue from postmortem brains of AD patients and age-matched controls, and prepare synaptosomes from that tissue. We then determine the amount of choline in the synaptosomes by means of a chemiluminescent assay. Preliminary experiments suggest that the AD synaptosomes do have more choline leakage than control synaptosomes. We are now performing additional experiments to determine whether the difference in choline leakage is significant.